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The Rgg1518 transcriptional regulator is a necessary facet of sugar metabolism and virulence in Streptococcus pneumoniae

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Version 2 2021-11-08, 14:19
Version 1 2021-10-15, 14:32
journal contribution
posted on 2021-11-08, 14:19 authored by Bushra Shlla, Ozcan Gazioglu, Sulman Shafeeq, Irfan Manzoor, Oscar P Kuipers, Andrew Ulijasz, N Luisa Hiller, Peter W Andrew, Hasan Yesilkaya
Rggs are a group of transcriptional regulators with diverse roles in metabolism and virulence. Here, we present work on the Rgg1518/SHP1518 quorum sensing system of Streptococcus pneumoniae. The activity of Rgg1518 is induced by its cognate peptide, SHP1518. In vitro analysis showed that the Rgg1518 system is active in conditions rich in galactose and mannose, key nutrients during nasopharyngeal colonization. Rgg1518 expression is highly induced in the presence of these sugars and its isogenic mutant is attenuated in growth on galactose and mannose. When compared with other Rgg systems, Rgg1518 has the largest regulon on galactose. On galactose it controls up- or downregulation of a functionally diverse set of genes involved in galactose metabolism, capsule biosynthesis, iron metabolism, protein translation, as well as other metabolic functions, acting mainly as a repressor of gene expression. Rgg1518 is a repressor of capsule biosynthesis, and binds directly to the capsule regulatory region. Comparison with other Rggs revealed inter-regulatory interactions among Rggs. Finally, the rgg1518 mutant is attenuated in colonization and virulence in a mouse model of colonization and pneumonia. We conclude that Rgg1518 is a virulence determinant that contributes to a regulatory network composed of multiple Rgg systems.

History

Citation

Molecular Microbiology, Volume 116, Issue 3, September 2021, Pages 996-1008

Author affiliation

Department of Respiratory Sciences, University of Leicester

Version

  • AM (Accepted Manuscript)

Published in

Molecular Microbiology

Publisher

Wiley

issn

0950-382X

eissn

1365-2958

Copyright date

2021

Available date

2022-08-10

Language

English